Safety of repeated trans-arterial radioembolization with multi-compartment dosimetry

Transarterial radioembolization (TARE) is one of the local treatment options for primary and metastatic liver tumors. However, our knowledge regarding the safety of repeated TARE remains limited. In this study, we aimed to evaluate the safety of repeated transarterial radioembolization with multi-compartment dosimetry.

In this retrospective single-center study, we analyzed the data of the patients who were treated with at least two separate sessions of radioembolization with ⁹⁰Y microspheres. Multi-compartment and voxel-wise dosimetry was performed for every treatment session and cumulative whole-liver normal tissue absorbed radiation dose (D_norm), V20-V100 values for whole-liver normal tissue were calculated. Toxicity was assessed with Common Terminology Criteria for Adverse Events (CTCAE) grading system for alanine aminotransferase (ALT)/aspartate aminotransferase (AST)/bilirubin levels and International Normalized Ratio (INR) before and after each treatment. In addition, albumin-bilirubin (ALBI) scores, grades, and changes in ALBI score (ΔALBI) were recorded. Difference between the ALBI scores before and after the treatment was compared with Wilcoxon tests, and relationships between ΔALBI and dosimetric variables were compared using linear regression analyses.

A total of 24 patients (6 males, 18 females; median age: 57 years) were included in the analysis. The most common diagnosis was colorectal carcinoma liver metastases (46%). Seventeen patients (71%) underwent two TARE treatments, five (21%) underwent three, and two (8%) underwent four. The median interval between the first and second treatments was 138 days (range: 34-782), and between the second and third treatments was 210 days (range: 72-435). No CTCAE Grade 3 or 4 toxicities were observed. ALBI score analysis revealed no significant changes after the first two treatments, but a significant difference was noted after the third treatment (P = 0.043), with one patient progressing to ALBI Grade 3 with significant hypoalbuminemia. No significant relationship was found between ΔALBI and treatment intervals. ALT/AST elevations were mostly transient and mild, with only one case of Grade 2 hepatotoxicity in each of the first two treatments. In patients treated with glass microspheres in their first two treatments (n = 12), a significant linear correlation was found between cumulative D_norm and ΔALBI (R² = 0.512, P = 0.007). Cumulative dose-volume histogram parameters, particularly V30, V40, and V50, showed significant correlations with ΔALBI. However, in patients treated with resin microspheres (n = 6), no statistically significant relationship was observed between cumulative D_norm and ΔALBI (P = 0.718).

Repeated TARE with a multi-compartment personalized dosimetric approach appears to be safe for the first two cycles, with limited low-grade toxicity. However, significant increase in ALBI scores after the third treatment was observed. ALBI score changes after second TARE were associated with cumulative liver radiation exposure in patients treated with glass microspheres. Larger studies are needed to further explore predictors of hepatotoxicity in repeated TARE.